Inclusion in an NLM database does not imply endorsement of, or agreement with, sharing sensitive information, make sure you’re on a federal University Professor (W3) for Cellular Immunology Additionally, some of the cultures were mixed with 8 × 104 unlabeled NK-sensitive K 562 cells (▪). Michael Heidelberger's studies of the immunochemistry of antibodies, antigen, and complement redefined the field of immunology and founded it on the precise, quantitative basis of analytical chemistry. No previous study analyzing the performance of a combination of CD2 × TA BsAb and CD2-trigger-Ab (36, 37, 38) had demonstrated that such a combination of Abs can induce cytotoxicity in resting PBMC. Epub 2018 Nov 27. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. FOIA Since Bordet, the term had referred to the heat-sensitive factors in serum that trigger cytolysis, the dissolution of antibody-coated cells. med. B, Human T lymphoblasts were incubated with saturating concentrations of mAbs or medium for 60 min at 4°C (first Ab). You also have the option to opt-out of these cookies. Your email address will not be published. B, Suboptimal stimulation by M1 and M2 allows further costimulation by CD58. Moreover, Heidelberger and Kendall's findings established that antigens and antibodies were multivalent, meaning that they could form two (in the case of antibodies) or more (in the case of antigens) chemical bonds with one another, bonds through which they combined into lattice-like structures. Pejnovic N, Jeftic I, Jovicic N, Arsenijevic N, Lukic ML. Curr Pharm Des. 8600 Rockville Pike (adsbygoogle = window.adsbygoogle || []).push({}); Proudly powered by WordPress This website uses cookies to improve your experience while you navigate through the website. Their experiments revealed three distinct zones within the solution in which the precipitin reaction between antigen and antibody unfolded: a zone of antibody excess, in which added polysaccharide antigen precipitated more antibody; an equivalent zone, in which neither antigen nor antibody could be found as all of them formed antigen-antibody complexes and precipitated out; if more antigen was added, a third zone could be detected in which precipitation of antibody nitrogen declined and antigens were in excess. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. A yield of purified BsAb of 20–30% based on the F(ab′)2 starting material was achieved and is demonstrated in Fig. From their theory Heidelberger and Kendall predicted that analytically pure antibody could be dissociated from polysaccharide-antibody precipitates through the use of strong salt. C. D. reports an unpaid position as Chairman of the WHO EYE (Eliminating Yellow Fever Epidemics) Laboratory Technical Working Group. © 2023 The American Association of Immunologists, Inc. For example, Heidelberger found that oxidized cotton contained multiple units of cellobiuronic acid, the same disaccharide of glucose and glucuronic acid contained in the capsular polysaccharides of type III and type VIII pneumococcus. Bethesda, MD 20894, Web Policies 2017 Jan;222(1):101-109, Moganti K, Li F, Schmuttermaier C, Riemann S, Klüter H, Gratchev A, Harmsen MC, Kzhyshkowska J J. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages. Potential effector cells expressing CD2 can be activated by pairs of monoclonal CD2 Abs, which leads to a vigorous proliferative response, massive cytokine production, and expression of cytolytic effector functions of both T lymphocytes and NK cells (3, 4). Riethmüller, G., E. Schneider-Gädicke, G. Schlimok, W. Schmiegel, R. Raab, K. Höffken, R. Gruber. When M1 and M2 were applied in combination, the final total Ab concentration was also 20 μg/ml. Cells were analyzed on a flow cytometer. In this regard, unlike several other costimulatory ligands (CD80, CD86, CD54), CD58 is expressed in the majority of tumor cells of various derivations investigated so far (26) and therefore could enhance the Ab-driven activation of different types of effector cells. 4Walter Gropiusstr. 2020 Feb 23;21(4):1525. doi: 10.3390/ijms21041525. Cultures were incubated for 16 h at 37°C in a 6% CO2 atmosphere to allow modulation before they were washed two times and incubated for 30 min at 4°C with biotinylated CD2 mAb ICRFCD2.8 (10 μg/ml) for detection of surface-CD2. Over twenty are known today. Fig. Using his trademark microanalytical techniques, Heidelberger demonstrated that complement added weight to immune precipitates, thereby deciding the long-standing dispute as to whether complement had actual substance, or was merely an unstable, colloidal, finely divided state of serum proteins. Immunobiology. Abs M1 (=AICD2.M1, IgG1), M2 (=AICD2.M2, IgG1), and AICD2.5 (IgG1) were produced in our laboratory. Several materials based on natural polymers for improved interaction with host tissue or surfaces that release anti-inflammatory drugs/bioactive agents have been developed for implant coating to reduce implant rejection. Freshly prepared PBMC were incubated for 16 h at 37°C with culture medium (A and B), CD2 mAb ICRFCD2.4 (IgM, 1:400 dilution of ascites) (C), BsAb M2xEGF-R (50 μg/ml), mAb M1 F(ab′)2 (50 μg/ml), and A 431 cells (D). Endler-Jobst, B., B. Schraven, B. Hutmacher, S. C. Meuer. The combination of mAbs M1 and M2 was selected and proved to be highly mitogenic for human T cells and PBMC. and JavaScript. The rationale behind this was that bispecific Abs used in, e.g., cancer treatment should not block important T cell functions involving the CD2-CD58 interaction, such as cell-cell adhesion, recirculation of T-lymphocytes as well as costimulation in the activation of T cells through CD2 (17, 19, 24). Proliferation assays showed that the M2 moiety in BsAb M2xEGF-R maintained its ability to stimulate lymphocytes in concert with M1(Fab′)2. 4 Eigenständige Forschungseinheit Translationale Molekulare Immunologie, Helmholtz Zentrum München, 81377 . A, PBMC or 6-day human PHA-blasts where incubated with saturating concentrations of individual mAbs as indicated in the figure. These unwanted reactions can be excluded for BsAbs with M1- or M2-specificity because these mAbs neither inhibit activation via TCR/CD3 (Fig. We have recently demonstrated that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support diabetes-associated inflammation and vascular complications. 2016 Apr 20. . 2020 Nov;73(5):1013-1022. doi: 10.1016/j.jhep.2020.05.047. Heidelberger administered formalin-killed sporozoites (the malarial parasites plasmodium vivax in their infective stage) between relapses of the disease, but the results were discouraging and the relapse rate was not reduced. 2023 Apr 21. doi: 10.1038/s41575-023-00771-6. The... Read More. Cultures of PBMC were incubated with 25 μl of Sepharose-coupled CD3 mAb OKT3 and the respective CD2 mAb. Subsequently, 2 × 107 sheep erythrocytes were added in a volume of 400 μl. PMCID: PMC9761887 DOI: 10.1093/cid/ciac580 Abstract The duration of protection after a single dose of yellow fever vaccine is a matter of debate. It is mandatory to procure user consent prior to running these cookies on your website. Data are expressed as percentage of specific lysis in a 4-h assay and represent means of triplicate cultures ± SD. F(ab′)2 fragments were purified by chromatography on protein A Sepharose. Please enable it to take advantage of the complete set of features! Maintained CD2 expression may enable T cells to bind further BsAb if a therapy with repeated administration of BsAb (35) is chosen. Springer Nature - PMC COVID-19 Collection. After having obtained purified antibodies in this way for the first time, they were able to show conclusively that they were protein, until then a matter of scientific dispute. -, Chen LH, Wilson ME. Dengler, T. J., J. C. Hoffmann, P. Knolle, M. Albert-Wolf, M. Roux, R. Wallich, S. C. Meuer. Similarly, by applying the precipitin curve and analyzing washed precipitates, Heidelberger was able to measure the amount of antigen in a biologic fluid, such as cerebrospinal fluid, by comparing it with the amount of antibody nitrogen precipitated, whose weight was known. By varying the dosage and routes of injection of the bacilli into rabbits, and by measuring the agglutinin antibody count of the sera produced by the rabbits in response to the inoculations, he was able to provide an antiserum with ten times more antibodies than existing ones. January 1990 . FOIA 2023 Mar 17. doi: 10.1038/s41575-023-00754-7. Resting human T cells were prepared as described in (5, 6) and were >95% reactive with CD3 mAbs. the contents by NLM or the National Institutes of Health. Meuer, S. C., R. E. Hussey, M. Fabbi, D. Fox, O. Acuto, K. A. Fitzgerald, J. C. Hodgdon, J. P. Protentis, S. F. Schlossman, E. L. Reinherz. Online ahead of print. Kanda T, Goto T, Hirotsu Y, Masuzaki R, Moriyama M, Omata M. Int J Mol Sci. J Immunol 15 August 1999; 163 (4): 2064–2072. The extent of waning of seroprotection after yellow fever vaccination depends on age and immune status at primary vaccination. High purity of the bispecific conjugate was demonstrated by chromatography on hydroxylapatite (data not shown) as well as in nonreducing SDS-PAGE (Fig. Several surface receptors expressed by immune effector cells have been suggested as targets for BsAbs such as Fc receptors on macrophages and neutrophils, the TCR/CD3 complex, and the CD2 and CD28 coreceptors (1). Performance of M1 and M2 in CD2- and CD3-driven proliferation of PBMC and T cells. Heidelberger focused on such immunological cross reactions for the next six decades because they allowed inferences about the chemical structure of polysaccharide antigens, and about how their structure determined their reactions with other antigens and with antibodies. Rev. Global Score 74.3 Global Score. After 7–10 days, no live PBMC and LAZ 509 cells could be detected, and the T cell clone was used for cytotoxicity assays. Riabov V, Salazar F, Htwe SS, Gudima A, Schmuttermaier C, Barthes J, Knopf-Marques H, Klüter H, Ghaemmaghami AM, Vrana NE, Kzhyshkowska J. Federal government websites often end in .gov or .mil. Importantly, effector cells are not activated during this “targeting phase” because they lack binding of the second CD2 Ab. In the late 1930s and early 1940s, Heidelberger extended his quantitative analytical method to the study of complement, a complex, essential component of host defense mechanisms against invading organisms. The percentage specific lysis was calculated as: 100 × [(experimental 51Cr release − SR)/(MR − SR)]. Curr Pharm Des. e-mail: immunologie(at)uni-hd.de By continuing to use our website, you are agreeing to, Flow cytometry and analysis of CD2 modulation, Anti-CD2 mAbs with a novel combination of characteristics, Binding properties and CD2-modulation by BsAb M2xEGF-R, BsAb M2xEGF-R mediates EGF-R-specific target cell lysis by a cytotoxic T cell clone, BsAb M2xEGF-R plus trigger Ab M1 activate resting PBMC for target cell lysis, BsAb M2xEGF-R plus trigger Ab M1 mediate cytotoxicity in a two-step protocol, https://doi.org/10.4049/jimmunol.163.4.2064. Correspondence to 7, 31535 Neustadt am Rübenberge. A. Kyewski. In these assays the BsAb has to be supplemented by the trigger Ab M1(Fab′)2 to achieve activation. The T cell clone C3F2 (11) (1 × 106 cells) was grown in the presence of 40 U/ml recombinant human IL-2 (Biotest, Dreieich, Germany), 1 × 106 freshly prepared human PBMC (irradiated with 60 Gy), and 1.5 × 105 EBV-transformed B-lymphoblastoid LAZ 509 cells (irradiated with 60 Gy). Flow cytometry studies of Ag recognition by mono- and bispecific Abs were conducted as described elsewhere (18). In some experiments unlabeled NK-sensitive K 562 cells were added additionally. 2015 Jan 15;194(2):709-18. Hands-on skills in epigenetic techniques such as ATAC-seq, ChIP-seq, or CUT…. Deutsches Krebsforschungszentrum Heidelberg, Abteilung Molekulare Immunologie, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany Fax: +49-6221-401629Search for more papers by this author April 1993 - March 1994. Values represent means of triplicate cultures ± SD. Jacobs, N., A. Mazzoni, D. Mezzanzanica, D. R. Negri, O. Valota, M. I. Colnaghi, M. Moutschen, J. Boniver, S. Canevari. With regard to the Ag on target cells, the EGF-R was chosen. MeSH After fifteen years at the Rockefeller Institute for Medical Research and one year at Mount Sinai Hospital, Heidelberger was offered a position--the first of its kind in the United States--as consulting research chemist to the Department of Medicine of the College of Physicians and Surgeons at Columbia University. C, Parental CD2 mAbs M1 and M2 do not interfere with the CD2-CD58 interaction in the erythrocyte rosetting of human T cells. That line moved towards unraveling the chemistry of pneumococcal and other bacterial and plant polysaccharides, and towards using them as factors in reactions that revealed the nature of other components of the immune system, in particular antibodies and complement. Thomas RE, Lorenzetti DL, Spragins W, Jackson D, Williamson T. Vaccine. Effect of hyperglycemia on Toll-like receptor-mediated inflammation. This site needs JavaScript to work properly. The principle that all of a given antigen is precipitated throughout the antibody excess and the equivalence zones was subsequently confirmed for other polysaccharide as well as for protein antigens by washing the precipitates and analyzing them for distinctive chemical constituents of the antigen. Further work during the 1890s revealed that in the presence of immune or antisera (sera that contained antibodies to specific diseases, which were obtained by inoculating animals such as rabbits with small doses of the disease-causing microorganism or toxin), bacteria clumped together or dissolved, and were thus rendered harmless. CD58 specificity of costimulation was proven by the addition of an anti-CD58 mAb, which abrogated the functional effect of recombinant CD58. Heidelberger and Kendall found that the highest rate of precipitation of antibody was found at the antigen excess end of the equivalent zone. Prof. (apl) Dr. rer. , and that the main problems of immunology would never be solved unless you could apply analytical microchemistry and get some real data in absolute units." Abbreviations used in this paper: BsAb, bispecific Ab; EGF-R, epidermal growth factor-receptor; TA, tumor Ag; TIL, tumor infiltrating lymphocyte; MLTC, mixed lymphocyte tumor culture; TNB, thio-bis-2-nitro-benzoic acid. The F(ab′)2 fragments of the triggering Ab M1 were generated by limited proteolysis with papain. These Ab constructs were derived from two novel CD2 mAbs, termed M1 and M2 that, together, but not individually activate T cells. Cultures (except A) were then incubated with biotinylated CD2 mAb ICRFCD2.8 (10 μg/ml), which could not be blocked by the Abs used in the previous incubation. Thus, most of the circulating BsAb is expected to be either localized or cleared by the time the trigger Ab is given. Briefly, Ab M2 and mAb 425 were converted into F(ab′)2 fragments by limited proteolysis with pepsin. Required fields are marked *. government site. The term immunochemistry was introduced by the Swedish physical chemist Svante Arrhenius in 1907 when he chose it as the title for a book of lectures, but he did so with apparent irony because so little was then known about the chemical reactions and structures of the immune system. 1 and Ref. 15 German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. Human T cells (2 × 105) were incubated with the respective mAb for 30 min at room temperature in a volume of 100 μl. -. Other CD2 mAbs, OKT11 (IgG1; Ortho, Neckargemünd, Germany), T112 (1OLD4C1, IgG2A), T113 (1 MONO2A6, IgG3; T112, and T113 were kindly provided by Dr. E. Reinherz, Dana-Farber Cancer Institute, Boston, MA), ICRFCD2.4 (IgM), ICRFCD2.5 (IgG2A), and ICRFCD2.8 (IgG2A; ICRF mAbs were kindly provided by Dr. M. Crumpton, Imperial Cancer Research Fund, London, U.K.). These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. Screening of CD2 specific hybridoma supernatants was done by measuring Ab binding to Jurkat T cells in cytometry analyses. Essential features of macrophages include their functional and phenotype diversity and plasticity that makes them attractive targets for the therapeutic programming. The simultaneous recruitment of T and NK cells as indicated by our in vitro experiments may provide the basis of an enhanced NK activity because T lymphocytes can strongly support NK functions by secreting IL-2. Further differences between CD2- and CD3-directed BsAbs exist: In CD3 × TA F(ab′)2 BsAbs the monovalency of the anti-CD3 moiety may cause problems because effective CD3-mediated T cell activation is dependent on cross-linking of CD3 molecules (39). Despite these practical advances and conceptual breakthroughs, however, the processes and physiological changes by which immunity was acquired were not understood until well into the 20th century. Many newly-discovered polysaccharide antigens were found to cross-react with anti-pneumococcal sera and polysaccharides prepared from diverse species of microorganisms of clinical significance, as well as from plant resins and gums. We examined whether there was also an excess of leukemia in patients after transplantation and whether this might be related to a particular immunosuppressive treatment. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment. All cultures in A–C (5 × 104 cells each) were grown for 72 h, pulsed with 37kBq [3H]thymidine, and harvested following 16 h of additional incubation. Accessibility A strong modulation of the CD2 receptor would not allow repeated binding of effector cells to targets nor would a second challenge with BsAb be able to target and activate such effector cells. All cultures had a final volume of 2 ml. -, Chalasani, N. et al. Inclusion Criteria: newly diagnosed acute lymphoblastic leukemia; age ≥ 1 year (> 365 days) and < 18 years old (up to 17 years old and 365 days) Their experiments further revealed the physiochemical heterogeneity of antibodies, which often combine in complex patterns in precipitating antisera (and may not precipitate with antigen when separated from other precipitating antibodies with which they are normally associated). You are using a browser version with limited support for CSS. Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease. Thank you for visiting nature.com. Often tumor cells have reduced surface densities of tumor Ags due to immunoselection (41) or modulation (42). Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1+ cDC1 as an important driver of liver pathology. Moreover, exposure of T cells to CD3 mAb alone can induce anergy (29). Clipboard, Search History, and several other advanced features are temporarily unavailable. Pimm, M. V., S. M. Andrew, R. W. Baldwin. J Travel Med 2019; 26:taz040. To unlock more data and access tools to help you get into your dream school, sign up for the U.S. News College Compass! . Immunogenicity and duration of protection after yellow fever vaccine in people living with human immunodeficiency virus: a systematic review. GRK1874/2 DIAMICOM. Cromium release was tested after an additional 6 h of culture. Activation of PBMC by BsAb M2xEGF-R plus trigger Ab M1 (Fab′)2 as observed in proliferation assays also induced the cytolytic effector function in resting T cells: Fig. https://www.who.int/publications/m/item/countries-with-risk-of-yellow-fe... WHO . government site. Accessibility The chemical mechanisms which led to agglutination (clumping together) and cytolysis (breaking open) of bacteria by antibodies were unclear. Galectin-3 and IL-33/ST2 axis roles and interplay in diet-induced steatohepatitis. With the entry of the United States into World War II, Heidelberger became involved in military research, particularly in efforts by the U.S. Army to immunize soldiers against pneumonia with pneumococcal polysaccharides, which Heidelberger predicted would trigger the production of antipneumococcal antibodies in humans (as it did in horses and rabbits). During treatment he measured the antibody content in patients' blood to test whether the solutions were effective, and adjusted the dosage accordingly. One concept to circumvent impaired effector-cell/tumor-cell interactions in malignant disease relates to the use of bispecific mAbs (BsAbs)3 that can simultaneously bind tumor cells and effector cells and activate the latter in a diseased organ. 2,C shows that several of the anti-CD2 mAbs tested, including mAbs T112 and T113, inhibit the in vitro activation of PBMC via the TCR/CD3 complex. E-mail address: m66@ix.urz.uni-heidelberg.de, Martin K. Wild, Wolfgang Strittmatter, Siegfried Matzku, Burkhart Schraven, Stefan C. Meuer; Tumor Therapy with Bispecific Antibody: The Targeting and Triggering Steps Can Be Separated Employing a CD2-Based Strategy. Knuth, A., T. Wölfel, E. Klehmann, T. Boon, K.-H. Meyer zum Buschenfelde. Hybridomas have been subcloned twice. Cytotoxicity assays with a CD8+ T cell clone showed that BsAb M2xEGF-R was able to target T cells to EGF-R-positive A 431 tumor cells with the bispecific conjugate being active at nanogram quantities. Tang Y, Bian Z, Zhao L, Liu Y, Liang S, Wang Q, Han X, Peng Y, Chen X, Shen L, Qiu D, Li Z, Ma X. Clin Exp Immunol. Purified T cells were incubated with M1 plus M2 (50 ng/ml) (bars to the left). -, Friedman, S. L., Neuschwander-Tetri, B. To investigate the targeting properties of BsAbs, cytotoxicity assays were conducted employing a cytotoxic CD8+ T cell clone (C3F2) (11). Moreover, primary macrophages exposed to the implantable materials ex vivo can be used to predict the individual patients’ reactions and allow selection of an optimal coating composition. Each well of a flat-bottom 24-well plate received 1 × 106 freshly prepared PBMC and the respective Abs in the concentrations as indicated. Specific lysis of A 431 cells was determined in a 4-h assay. Heidelberger and his first graduate student and long-time Columbia University colleague, Elvin A. Kabat (1914-2000), subsequently extended this quantitative theory to agglutination, the clumping together of antigen-bearing cells, microorganisms, or particles in suspension by the introduction of specific antibodies (agglutinins). 9). Rosetting can be reduced by binding of certain CD2 mAbs to the CD2 molecule. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Vaccines and vaccination against yellow fever. We made use of a human allogeneic system employing the EGF-R-positive C8161 melanoma cell line as target along with MLTC-derived freshly prepared tumor infiltrating lymphocytes. Bethesda, MD 20894, Web Policies Perhaps more importantly, when compared with the widely used targeting to the CD3 complex, the M1- and M2-based targeting of the CD2 molecule may have a critical advantage: previous in vitro studies have shown that binding of CD3 × TA BsAbs to CTL can lead to the inability of these cells to carry out a TCR-specific target cell lysis (27). MeSH At least 300 T cells were counted per culture and were considered as rosetted when bound by at least three erythrocytes. In our meta-analysis, we used random-effects models. 2016 Jul 22. pii: S0171-2985(16)30325-4. doi: 10.1016/j.imbio.2016.07.006. In such cases the combination of a CD2 × TA BsAb and trigger CD2 mAb may be more efficient because binding of two different CD2 Abs provides both signals required for T cell activation (45). Unable to load your collection due to an error, Unable to load your delegates due to an error. of the Faculty of Medicine, Heidelberg University, Germany, Member of the Research Board of the Faculty of Medicine, Heidelberg University, Germany, Member of the PhD committee (Dr. sc. BsAb M2xEGF-R plus trigger Ab M1 mediate cytotoxicity in a two-step protocol. The .gov means it’s official. 4 ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA. Law, A. J. McKnight, M. G Tomlinson, P. A. van der Merwe. Using pneumococcal polysaccharides, by then produced in commercial quantities by Squibb, Heidelberger and his collaborators Colin MacLeod (who, with Avery and Maclyn McCarty, had discovered that DNA was the chemical substance of heredity) and Richard G. Hodges were able to report that recipients received protection against four types of pneumonia, whereas soldiers in a control group continued to show incidences of these types of pneumonia. Such phagocytic cells, it was soon suggested, required that bacteria be coated by antibody before they could effectively kill them. In this work a time range of up to 12 h has been tested in vitro (Fig. 9,A shows that dose dependently the combination of BsAb M2xEGF-R plus M1 (Fab′)2, when added simultaneously, induced tumor cell lysis while the individual reagents did not. The efficiency of this TIL driven melanoma specific lysis was similar as for the PBMC/A431 system situation (compare Fig. 2016 Jul 29;7:12343. The site is secure. Immune rats contained lymphocytes able to specifically lyse CD modified as well as unmodified AS tumor cells in vitro, most likely contributing to the in vivo antitumoral reaction. He was "convinced that it was necessary for progress in immunology to have some better methods than just titrations and dilution end points . J Travel Med. sharing sensitive information, make sure you’re on a federal Scott, C. F., W. A. Blättler, J. M. Lambert, R. S. Kalish, C. Morimoto, S. F. Schlossman.
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